Activation of opioid receptors by exogenous opioid drugs may modify motility. Our pilot studies indicate that LAAM, an opioid agonist which is given three-times-per-week (t.i.w.) in the treatment of former heroin addicts, may stimulate human motility on days of administration and/or suppress motility on in-between days. The measured effect was of considerable magnitude and might constitute a behavioral toxicity of this treatment. The study suggested that assessments of behavioral toxicity from LAAM should employ an administration-day vs. day-off design. We here propose to replicate (or refute) that finding in better designed studies using monkeys and patients. In addition the proposed studies will seek LAMM-induced daily fluctuations in mood and social (including sexual) behavior which may occur concomitantly with these motility changes. Accumulating evidence for physiological and behavioral activity of opioid antagonists, such as naltrexone, suggests that blocking the actions of endogenous opioid peptides also may have behavioral consequences. Naltrexone also, like LAMM, is administered t.i.w. to former heroin addicts, and we propose to examine its effects on day-to-day fluctuations of human motility and social behavior in man and monkey, and on human mood. The design of naltrexone studies will be similar to those of LAAM studies, providing comparison of potential behavioral side effects from the two treatments. As in our previous studies, motility will be monitored around the clock from human beings via sophisticated electronic actometers with solid state memories, and from monkey social groups via FM telemetry. Studies will include administration-day vs. day-off comparisons of drug effects on motility and social behavior (man and monkey) and on mood (man) during chronic t.i.w. LAAM and t.i.w. naltrexone treatment, together with an acute dose-response study of naltrexone in monkeys. This re-submission of DA02386 responds to reviewers' questions about the original application. We now have demonstrated reliability and validity for our actometers, and we have improved experimental control over our subjects by obtaining our own IND's. Moreover we now plan to consider tolerance through both long- and short-term studies of LAAM and naltrexone.